The IRCM
Research
The Clinic
Studying at IRCM
Core facilities
Conferences
Careers
Mechanisms of Genetic Diversity
Skip navigation links
Director
Team
Projects
Publications
Available positions
Contact us


Home > Mechanisms of Genetic Diversity > Available positions
Home > Mechanisms of Genetic Diversity > Available positions
Research unit director
Available positions

Post-doctoral position at the Laboratory of mechanisms of genetic diversity

Exploiting B cell biology to target B cell lymphoma

A large proportion of non-Hodgkin lymphomas become resistant to the available therapies, so new alternatives are needed. This project will exploit a vulnerability created by the enzyme Activation induced deaminase (AID) in B cell lymphoma and leukemia, to specifically target these cancer cells. The project is based on the observations that ablating the non-essential DNA repair factor Uracil N-glycosylase (UNG) allows AID to produce catastrophic damage at the telomeres,
permanently arresting B cell proliferation (Cortizas et al, 2016). The project will :

  1. Use human B cell lymphoma-derived cells in vitro to find the mechanisms leading to cell
    death and/or cell proliferation arrest in AID+ UNG-deficient cells depending on the AID
    levels, telomerase activity and the status of p53-dependent apoptotic pathway.
  2. Establish mouse models of B cell lymphoma to validate the approach in vivo.
  3. Develop UNG inhibitors for pre/clinical research.

The project is funded by the Lymphoma and leukemia society of Canada starting in July 2017.

We are looking for a candidate with a recent PhD that have demonstrable experience in the relevant techniques necessary for the project (cell culture, transfection techniques, mouse work) and excellent organizational and communicational skills. Previous experience in immunology or hematological malignancies would be an advantage.

Please, send a statement of interest, CV and two letters of reference (including one from PhD supervisor) to Dr. Javier M Di Noia (javier.di.noia@ircm.qc.ca).

 

References

Cortizas, E. M.*, Zahn, A.*, Safavi, S.*, Reed, J. A., Vega, F., Di Noia, J. M.*, & Verdun, R. E.* (2016). UNG protects B cells from AID-induced telomere loss. The Journal of Experimental Medicine, 213(11), 2459–2472.

Zahn, A., Daugan, M., Safavi, S., Godin, D., Cheong, C., Lamarre, A., & Di Noia, J. M. (2013). Separation of Function between Isotype Switching and Affinity Maturation In Vivo during Acute Immune Responses and Circulating Autoantibodies in UNGDeficient Mice. Journal of Immunology, 190(12), 5949–5960.

 

Other recent work by the lab

Methot et al. (2015). Consecutive interactions with HSP90 and eEF1A underlie a functional maturation and storage pathway of AID in the cytoplasm. The Journal of Experimental Medicine, 212(4), 581–596.

Montamat-Sicotte et al. (2015). HSP90 inhibitors decrease AID levels and activity in mice and in human cells. European Journal of Immunology, 45(8), 2365–2376.

Zahn et al. (2014). Activation induced deaminase C-terminal domain links DNA breaks to end protection and repair during class switch recombination. Proceedings of the National Academy of Sciences of the United States of America, 111(11), E988–97.

All rights reserved: IRCM 2011_110 avenue des Pins Ouest - Montréal (Québec) H2W 1R7 – Canada
.